Guido Rychen

Update: use of the benchmark dose approach in risk assessment

Abstract The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the NOAEL approach for deriving a Reference Point (RP). Most of the modifications made to the SC guidance of 2009 concern the section providing guidance on how to apply the BMD approach. Model averaging is recommended as the preferred method for calculating the BMD confidence interval, while acknowledging that the respective tools are still under development and may not be easily accessible to all. Therefore, selecting or rejecting models is still considered as a suboptimal alternative. The set of default models to be used for BMD analysis has been reviewed, and the Akaike information criterion (AIC) has been introduced instead of the log‐likelihood to characterise the goodness of fit of different mathematical models to a dose–response data set. A flowchart has also been inserted in this update to guide the reader step‐by‐step when performing a BMD analysis, as well as a chapter on the distributional part of dose–response models and a template for reporting a BMD analysis in a complete and transparent manner. Finally, it is recommended to always report the BMD confidence interval rather than the value of the BMD. The lower bound (BMDL) is needed as a potential RP, and the upper bound (BMDU) is needed for establishing the BMDU/BMDL per ratio reflecting the uncertainty in the BMD estimate. This updated guidance does not call for a general re‐evaluation of previous assessments where the NOAEL approach or the BMD approach as described in the 2009 SC guidance was used, in particular when the exposure is clearly smaller (e.g. more than one order of magnitude) than the health‐based guidance value. Finally, the SC firmly reiterates to reconsider test guidelines given the expected wide application of the BMD approach.

Guidance on the use of the weight of evidence approach in scientific assessments

Abstract EFSA requested the Scientific Committee to develop a guidance document on the use of the weight of evidence approach in scientific assessments for use in all areas under EFSAs remit. The guidance document addresses the use of weight of evidence approaches in scientific assessments using both qualitative and quantitative approaches. Several case studies covering the various areas under EFSAs remit are annexed to the guidance document to illustrate the applicability of the proposed approach. Weight of evidence assessment is defined in this guidance as a process in which evidence is integrated to determine the relative support for possible answers to a question. This document considers the weight of evidence assessment as comprising three basic steps: (1) assembling the evidence into lines of evidence of similar type, (2) weighing the evidence, (3) integrating the evidence. The present document identifies reliability, relevance and consistency as three basic considerations for weighing evidence.

Guidance on Uncertainty Analysis in Scientific Assessments

Abstract Uncertainty analysis is the process of identifying limitations in scientific knowledge and evaluating their implications for scientific conclusions. It is therefore relevant in all EFSAs scientific assessments and also necessary, to ensure that the assessment conclusions provide reliable information for decision‐making. The form and extent of uncertainty analysis, and how the conclusions should be reported, vary widely depending on the nature and context of each assessment and the degree of uncertainty that is present. This document provides concise guidance on how to identify which options for uncertainty analysis are appropriate in each assessment, and how to apply them. It is accompanied by a separate, supporting opinion that explains the key concepts and principles behind this Guidance, and describes the methods in more detail.

Guidance on the risk assessment of substances present in food intended for infants below 16 weeks of age

Abstract Following a request from the European Commission to EFSA, the EFSA Scientific Committee (SC) prepared a guidance for the risk assessment of substances present in food intended for infants below 16 weeks of age. In its approach to develop this guidance, the EFSA SC took into account, among others, (i) an exposure assessment based on infant formula as the only source of nutrition; (ii) knowledge of organ development in human infants, including the development of the gut, metabolic and excretory capacities, the brain and brain barriers, the immune system, the endocrine and reproductive systems; (iii) the overall toxicological profile of the substance identified through the standard toxicological tests, including critical effects; (iv) the relevance for the human infant of the neonatal experimental animal models used. The EFSA SC notes that during the period from birth up to 16 weeks, infants are expected to be exclusively fed on breast milk and/or infant formula. The EFSA SC views this period as the time where health‐based guidance values for the general population do not apply without further considerations. High infant formula consumption per body weight is derived from 95th percentile consumption. The first weeks of life is the time of the highest relative consumption on a body weight basis. Therefore, when performing an exposure assessment, the EFSA SC proposes to use the high consumption value of 260 mL/kg bw per day. A decision tree approach is proposed that enables a risk assessment of substances present in food intended for infants below 16 weeks of age. The additional information needed when testing substances present in food for infants below 16 weeks of age and the approach to be taken for the risk assessment are on a case‐by‐case basis, depending on whether the substance is added intentionally to food and is systemically available.

Guidance on the assessment of the biological relevance of data in scientific assessments

Abstract EFSA requested its Scientific Committee to prepare a guidance document providing generic issues and criteria to consider biological relevance, particularly when deciding on whether an observed effect is of biological relevance, i.e. is adverse (or shows a beneficial health effect) or not. The guidance document provides a general framework for establishing the biological relevance of observations at various stages of the assessment. Biological relevance is considered at three main stages related to the process of dealing with evidence: Development of the assessment strategy. In this context, specification of agents, effects, subjects and conditions in relation to the assessment question(s): Collection and extraction of data; Appraisal and integration of the relevance of the agents, subjects, effects and conditions, i.e. reviewing dimensions of biological relevance for each data set. A decision tree is developed to assist in the collection, identification and appraisal of relevant data for a given specific assessment question to be answered.

Scientific motivations and criteria to consider updating EFSA scientific assessments

Abstract EFSA is committed to assess and communicate the risks occurring in the food and feed chain from farm to fork and to provide other forms of scientific advice. This work, carried out by EFSA since its inception, has resulted in the adoption of thousands of scientific assessments. EFSA is obliged to re‐assess past assessments in specific regulatory contexts such as those on food and feed additives, active substances in plant protection products and genetically modified food and feed. In other sectors, the consideration for updating past EFSA scientific assessments is taken on an ad hoc basis mainly depending on specific requests by risk managers or on EFSA self‐tasking. If safety is potentially at stake in any area within EFSAs remit, the readiness to update past scientific assessments is important to keep EFSA at the forefront of science and to promote an effective risk assessment. Although this task might be very complex and resource demanding, it is fundamental to EFSAs mission. The present EFSA Scientific Committee opinion deals with scientific motivations and criteria to contribute to the timely updating of EFSA scientific assessments. It is recognised that the decision for updating should be agreed following careful consideration of all the relevant elements by the EFSA management, in collaboration with risk managers and stakeholders. The present opinion addresses the scientific approaches through which it would be possible for EFSA to increase the speed and effectiveness of the acquisition of new data, as well as, to improve the consequent evaluations to assess the relevance and reliability of new data in the context of contributing to the better definition of whether to update past scientific assessments.

Safety and efficacy of Lactobacillus buchneri NRRL B-50733 as a silage additive for all animal species

Abstract Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), was asked to deliver a scientific opinion on the safety and efficacy of a strain of Lactobacillus buchneri when used as a technological additive intended to improve ensiling at a proposed application rate of 1 × 108 colony forming units (CFU)/kg fresh material. The bacterial species L. buchneri is considered by EFSA to be suitable for the qualified presumption of safety approach to safety assessment. As the identity of the strain has been clearly established and as no antibiotic resistance of concern was detected, the use of the strain as a silage additive is considered safe for livestock species, for consumers of products from animals fed the treated silage and for the environment. In the absence of data, no conclusion can be drawn on the skin and eye irritancy or skin sensitisation of the additive. The additive should be considered a potential respiratory sensitiser. Three studies with laboratory‐scale silos were made using samples of easy, moderately difficult and difficult to ensile material. In each case, replicate silos containing untreated forage were compared with identical silos containing the same forage treated with the combination of Lactobacillus buchneri NRRL B‐50733 at an intended concentration of 1 × 108 CFU/kg fresh matter. The results showed that the addition of Lactobacillus buchneri NRRL B‐50733 at 1 × 108 CFU/kg fresh material has the potential to improve the aerobic stability of silage with a dry matter content ranging from 30% to 73%.

Safety and efficacy of secondary aliphatic saturated or unsaturated alcohols, ketones, ketals and esters with a second secondary or tertiary oxygenated functional group belonging to chemical group 10 when used as flavourings for all animal species

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of 11 compounds belonging to chemical group 10. They are currently authorised as flavours in food. The FEEDAP Panel concludes that: diacetyl [07.052] is safe at the proposed maximum use level of 25 mg/kg complete feed for all target species, except piglets, chickens for fattening, laying hens and cats, for which the proposed normal use level of 5 mg/kg is safe; 3-hydroxybutan-2-one [07.051], 3-methylcyclo-pentan-1,2-dione [07.056], 3ethylcyclopentan-1,2-dione [07.057], pentan-2,3-dione [07.060], 3,4-dimethylcyclopentan-1,2-dione [07.075], 3,5-dimethyl cyclopentan-1,2-dione [07.076], hexan-3,4-dione [07.077] and sec-butan-3-onyl acetate [09.186] are safe at the proposed maximum dose level of 5 mg/kg for all target species; 2,6,6-trimethylcyclohex-2-en1,4-dione [07.109] and 3-methylnona-2,4-dione [07.184] are safe only at concentrations below the proposed use levels (0.5 mg/kg for cattle, salmonids and non-food producing animals, and 0.3 mg/kg for pigs and poultry). No safety concern would arise for the consumer from the use of these compounds up to the highest proposed level in feeds. Hazards for skin and eye contact and respiratory exposure are recognised for the majority of the compounds under application. Most are classified as irritating to the respiratory system. For 3hydroxybutan-2-one [07.051], diacetyl [07.052], pentan-2,3-dione [07.060], hexan-3,4-dione [07.077], 2,6,6trimethylcyclohex-2-en-1,4-dione [07.109], 3-methylnona-2,4-dione [07.184] and sec-butan-3-onyl acetate [09.186], the maximum proposed use levels are considered safe for the environment. For cyclopentanediones (3-methylcyclopentan-1,2-dione [07.056], 3-ethylcyclopentan-1.2-dione [07.057], 3,4 dimethylcyclopentan1,2-dione [07.075] and 3,5-dimethylcyclopentan-1,2-dione [07.076]) usage at levels up to 0.5 mg/kg feed is unlikely to have an adverse effect on the terrestrial or freshwater environments. Because all the compounds under assessment are used in food as flavourings and their function in feed is essentially the same as that in food, no further demonstration of efficacy is necessary.

Safety and efficacy of selenium‐enriched yeast (Saccharomyces cerevisiae CNCM I‐3399) for all animal species

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of selenium‐enriched yeast (Saccharomyces cerevisiae CNCM I‐3399) for all animal species, based on a dossier submitted for the modification of the terms of authorisation of the additive. The additive is currently authorised as selenomethionine produced by S. cerevisiae CNCM I‐3399 as a nutritional additive (compound of trace elements) with a minimum selenium content of 2,000 mg/kg. The applicant proposed the inclusion of an additional formulation with a minimum content of selenium in the additive of 3,000 mg/kg. Considering (i) that there are no relevant changes in the manufacturing of the product compared to the former application and (ii) that the conditions of use already authorised remain the same, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) stated that the modification requested would not affect the conclusions of the FEEDAP Panel on safety for the consumer, safety for the environment and efficacy of the product made in a previous assessment of a similar product with a lower selenium concentration. Since the capacity of the additive to homogeneously distribute in feed was proven, the tolerance studies already provided for the currently authorised product could be used to conclude on the safety of the additive for the target animals. Selenium is hazardous upon inhalation; owing to the dusting potential and the selenium content of dust, persons handling the additive are at risk. The additive should be considered as a respiratory sensitiser. The additive is not an irritant for eyes and skin. No conclusions can be reached on the dermal sensitising properties of the additive.